This invention relates to methods for diagnosing both latent and active cancers. More specifically, this invention relates to methods for diagnosing cancers by detecting the presence and relative amounts of isoforms of A-protein in a subject.
A-protein is a cellular enzyme that was first isolated from vertebrate rod photoreceptor cells by Schmidt et al., Invest. Opthalmol. Vis. Sci., 24:244 (1983). A-protein is also known in the scientific literature by the names GP, Cockcroft, Trends Biochem. Sci., 12:75-78 (1987); recoverin Dizhoor et al., J Biol. Chem., 267:16033-16036 (1992); and CAR protein, Thirkill et al., Arch. Opthalmol., 111:974-978 (1993). A-protein has been characterized as a GTP-binding protein (g-protein), Schmidt et al., Invest. Opthalmol. Vis. Sci., 28:94 (1987), that regulates phosphinositide metabolism by activating phospholipase C, Schmidt et al., Invest Opthalmol. Vis. Sci., 29:123 (1988).
A-protein exists in two forms; Schmidt et al., Invest. Opthalmol. Vis. Sci., 30:172 (1989); and Dizhoor et al., J. Biol. Chem., 267:16033-16036 (1992): as a monomer of 26,000 daltons which is soluble in the cytosol, and as a co-synthetically modified form to which a fatty acid is attached by the action of the enzyme N-myristoyl transferase (NMT; E.C.2.3.1.97). The modified form of A-protein tends to self-associate as stable pentameric homopolymers with an approximate molecular weight of 130,000 daltons. These homoploymers are peripherally bound to the inner aspect of the cell membrane.
In its peripherally membrane-bound form, A-protein is activated by a growth-factor receptor imbedded in the plasmalemma subsequent to activation of the receptor by a growth factor. The activation of this metabolic cascade mechanism results in a sustained release of calcium into the cytosol which ultimately stimulates the cell to divide. This general scheme is referred to as signal transduction (see U.S. Pat. No. 5,100,661).
In non-ocular tissues, A-protein transduces growth signals and is expressed in mitotically active cells including malignant tissues. A-protein is expressed inside affected malignant cells and in the blood stream. Fragments of the protein are also displayed on the surface of malignant cells. See Thirkill et al., Invest. Opthalmol. Vis. Sci., 33:2768-2772 (1992).
U.S. Patent Publication No. 20070053893, published Mar. 8, 2007, to Schmidt, discloses a method for reducing immunological tolerance to malignancy using formulations of myristoylCoA and N-myristoyl transferase to treat carcinomas displaying A-protein.
It will be readily appreciated that there exists a need for new and improved methods for diagnosing both potential or latent cancers and actual malignancies which may be difficult to detect using conventional diagnostic tools.